PAMP) for example lipopolysaccharide (LPS) and CpG-containing oligonucleotides (CpG ODN). TLR2 and TLR4 are main receptors for Gram-positive and Gram-negative bacterial cell wall elements, respectively. TLR9 is required for CpG signalling. LPS or CpG ODN can activate immature dendritic cells (DC) and induce DC maturation characterized by production of cytokines, up-regulation of co-stimulatory molecules, and improved capability to activate T cells. On the other hand, tiny is identified regarding the regulation of TLR gene expression in mouse DC. Within this study, we investigated the regulation of TLR2, TLR4 and TLR9 gene expression by LPS in murine immature DC. TLR2, TLR4 and TLR9 mRNA were up-regulated following LPS stimulation. The up-regulation of TLR9 expression coincided with considerably enhanced production of tumour necrosis factor-a induced by LPS plus CpG ODN. Whilst inhibition of extracellular signal-related kinase and NF-kB activation suppressed the up-regulation with the expression of TLR2, TLR4 and TLR9 mRNA, inhibition of p38 kinase prevented the up-regulation of TLR2 and TLR4 mRNA expression but enhanced the up-regulation of TLR9 expression. These final results demonstrated that TLR2, TLR4 and TLR9 gene expression was differently regulated by LPS in mouse immature DC. Up-regulation of TLR2, TLR4 and TLR9 expression by LPS could possibly market the overall responses of DC to bacteria and assistance to explain the synergy among LPS and also other bacterial solutions in the induction of cytokine production.2832911-62-1 In stock INTRODUCTION Dendritic cells (DC), because the most potent specialist antigen-presenting cells, are vital sentinels in antimicrobial immune responses. Microbial solutions, for instance lipopolysaccharide (LPS) and bacterial DNA, can activateReceived three July 2001; revised 21 January 2002; accepted 30 January 2002. Abbreviations: CpG ODN, CpG-containing oligonucleotides; DC, dendritic cells; ERK, extracellular signal-regulated kinase; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; PAMP, pathogen-associated molecule patterns; PDTC, pyrrolidinecarbodithioic acid; TLR, toll-like receptor. Correspondence: Dr Xuetao Cao, Institute of Immunology, Second Military Healthcare University, 800 Xiangyin Road, Shanghai 200433, China.3-Methoxy-1H-indole Chemscene E-mail: caoxt@public3.PMID:23907521 sta.net.cnimmature DC and induce DC maturation, characterized by production of cytokines, up-regulation of co-stimulatory molecules and enhanced capability to activate T cells.1 Cells in the innate immune technique use a number of pathogenassociated molecule pattern (PAMP) recognition receptors to recognize the patterns shared between pathogens.1,2 Nonetheless, the mechanisms by which the microbial solutions are recognized by immune cells and also the signals are transmitted to induce downstream events haven’t been completely understood. Recently, Toll-like receptors (TLR) have been identified as big recognition receptors for PAMP including LPS, peptidoglycan, lipoteichoic acid and CpG-containing oligonucleotides (CpG ODN).three? Toll, initial identified as a crucial protein controlling dorsoventral pattern formation throughout the early improvement of Drosophila melanogaster, is usually a transmembrane protein whose intracellular portion#2002 Blackwell Science LtdRegulation of TLR expression by LPS in DCis homologous to that of interleukin-1 receptor (IL-1R) family proteins.six It has been shown that Toll participates in antimicrobial immune responses in adult Drosophila.7 Activation of Toll final results within the initiation of a signalling cascade homologous to that activa.